RESUMO
OBJECTIVES: To determine the safety, tolerability, pharmacokinetics, and immunomodulatory effects of a 6-week course of atorvastatin in patients with acute Kawasaki disease with coronary artery (CA) aneurysm (CAA). STUDY DESIGN: This was a Phase I/IIa 2-center dose-escalation study of atorvastatin (0.125-0.75 mg/kg/day) in 34 patients with Kawasaki disease (aged 2-17 years) with echocardiographic evidence of CAA. We measured levels of the brain metabolite 24(S)-hydroxycholesterol (24-OHC), serum lipids, acute-phase reactants, liver enzymes, and creatine phosphokinase; peripheral blood mononuclear cell populations; and CA internal diameter normalized for body surface area before atorvastatin treatment and at 2 and 6 weeks after initiation of atorvastatin treatment. RESULTS: A 6-week course of up to 0.75 mg/kg/day of atorvastatin was well tolerated by the 34 subjects (median age, 5.3 years; IQR, 2.6-6.4 years), with no serious adverse events attributable to the study drug. The areas under the curve for atorvastatin and its metabolite were larger in the study subjects compared with those reported in adults, suggesting a slower rate of metabolism in children. The 24-OHC levels were similar between the atorvastatin-treated subjects and matched controls. CONCLUSIONS: Atorvastatin was safe and well tolerated in our cohort of children with acute Kawasaki disease and CAA. A Phase III efficacy trial is warranted in this patient population, which may benefit from the known anti-inflammatory and immunomodulatory effects of this drug.
Assuntos
Atorvastatina/administração & dosagem , Aneurisma Coronário/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Administração Oral , Adolescente , Atorvastatina/efeitos adversos , Atorvastatina/farmacocinética , Criança , Pré-Escolar , Aneurisma Coronário/etiologia , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacocinética , Masculino , Síndrome de Linfonodos Mucocutâneos/complicaçõesRESUMO
OBJECTIVES: To assess the prevalence of superantigen secreting bacteria in children with acute Kawasaki disease (KD) relative to control patients. STUDY DESIGN: Bacterial cultures were obtained in a blinded fashion from the throat, rectum, and groin of 45 patients with untreated acute KD and 37 febrile control patients from 6 centers in the United States. Cultures were processed for the presence of superantigen-producing bacteria at a central laboratory. RESULTS: Staphylococci or streptococci that produced superantigens (TSST-1, SEB, SEC, SPEB, SPEC) were isolated from 25 of 45 patients with KD (56%) as compared with 13 of 37 (35%) control patients (P =.078). Because SEB- and SEC-producing Staphylococcus aureus have not been associated with KD and because they do not induce a Vbeta2+ T-lymphocyte response, we analyzed the difference between groups relative to superantigens TSST-1 or SPEB/SPEC production. TSST-1 secreting S aureus or SPEB/SPEC producing group A streptococci were isolated from 20 of 45 (44%) patients with KD compared with 7 of 37 (19%) control patients (P =.019). CONCLUSIONS: The overall isolation rates of superantigen (TSST-1, SPEB, SPEC, SEB, SEC) producing bacteria between patients with KD and febrile control patients were not statistically significant. However, future studies should further examine the potential role of Vbeta2-stimulatory superantigens (TSST-1 and SPEB/SPEC) in KD.